Inflammatory neurodegeneration induced by lipoteichoic acid from Staphylococcus aureus is mediated by glia activation, nitrosative and oxidative stress, and caspase activation
Inflammatory neurodegeneration induced by lipoteichoic acid from Staphylococcus aureus is mediated by glia activation, nitrosative and oxidative stress, and caspase activation
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DOI：
10.1111/j.1471-4159.2005.03422.x
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发表时间：
2005-11-01
影响因子：
4.7
通讯作者：
Bal-Price, A
中科院分区：
文献类型：
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作者：
Kinsner, A;Pilotto, V;Bal-Price, A
在这项研究中，我们研究了由脂磷壁酸（LTA）和胞壁酰二肽（MDP）从革兰氏阳性细菌细胞壁诱导的神经元细胞死亡的机制，使用原代培养的大鼠小脑颗粒细胞（CGC）和大鼠皮质胶质细胞（星形胶质细胞和小胶质细胞）。来自金黄色葡萄球菌的LTA（+/- MDP）诱导两种类型神经胶质细胞的强烈炎症反应（释放白细胞介素-1 β、肿瘤坏死因子-α和一氧化氮）。CGC的死亡是由活化的神经胶质引起的，因为在没有神经胶质的情况下（用7.5 μ M胞嘧啶-D-阿拉伯糖苷处理以抑制非神经元细胞增殖），LTA + MDP没有引起显著的细胞死亡（小于20%）。此外，罗丹明标记的LTA染色证实，LTA仅与小胶质细胞和星形胶质细胞（而不是神经元）结合。诱导型一氧化氮合酶抑制剂可部分阻断LTA（+/- MDP）激活的胶质细胞诱导的神经细胞死亡（1400 W; 100 μ M），并完全阻断了超氧化物歧化酶模拟物[锰（III）四（4-苯甲酸）氯化卟啉; 50 μ M]和过氧亚硝酸根清除剂[5，10，15，20-四（4-sulfonatophenyl）porphyrinato铁（III）; 100 μ M]表明一氧化氮和过氧亚硝酸盐有助于LTA诱导的细胞死亡。此外，神经元细胞死亡被半胱天冬酶-3（z-DEVD-fetamine; 50 μ M）和半胱天冬酶-8（z-Ile-Glu（O-Me）-Thr-Asp（O-Me）fluoromethyl ketone; 50 μ M）的选择性抑制剂抑制，表明它们参与LTA诱导的神经元细胞死亡
In this study we investigated the mechanisms of neuronal cell death induced by lipoteichoic acid (LTA) and muramyl dipeptide (MDP) from Gram-positive bacterial cell walls using primary cultures of rat cerebellum granule cells (CGCs) and rat cortical glial cells (astrocytes and microglia). LTA (+/- MDP) from Staphylococcus aureus induced a strong inflammatory response of both types of glial cells (release of interleukin-1 beta, tumour necrosis factor-alpha and nitric oxide). The death of CGCs was caused by activated glia because in the absence of glia (treatment with 7.5 mu M cytosine-D-arabinoside to inhibit non-neuronal cell proliferation) LTA + MDP did not cause significant cell death (less than 20%). In addition, staining with rhodamine-labelled LTA confirmed that LTA was bound only to microglia and astrocytes (not neurones). Neuronal cell death induced by LTA (+/- MDP)-activated glia was partially blocked by an inducible nitric oxide synthase inhibitor (1400 W; 100 mu M), and completely blocked by a superoxide dismutase mimetic [manganese (III) tetrakis (4-benzoic acid)porphyrin chloride; 50 mu M] and a peroxynitrite scavenger [5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato iron (III); 100 mu M] suggesting that nitric oxide and peroxynitrite contributed to LTA-induced cell death. Moreover, neuronal cell death was inhibited by selective inhibitors of caspase-3 (z-DEVD-fmk; 50 mu M) and caspase-8 (z-Ile-Glu(O-Me)-Thr-Asp(O-Me) fluoromethyl ketone; 50 mu M) indicating that they were involved in LTA-induced neuronal cell death